Liver Stem Cell Populations

- Hepatic Stem Cells: In Search of

The vast majority of liver-related stem cell research has focusedon either fetal-derived hepatic stem cells or oval cells. Theoval cell is typically defined as a unique cellular populationthat is generated from the biliary compartment in response tohepatic injury [3–8]. To complement the ongoing researchefforts involving these two populations, several investigatorshave more recently identified and isolated hepatic progenitorcells from adult tissue. These cells, like their embryonic counterparts,can be bipotent and are capable of multiple rounds of cell division[9, 10]. The nomenclature and function of described liver-relatedstem cell populations, including the progenitor cell populations,remains an area of dispute, as the majority of these cellularpopulations have not been used in a therapeutic approach toprovide organ-associated function. To further complicate thechallenge with nomenclature, adult liver stem cells are oftenreferred to as hepatic progenitor cells, hepatic oval cells,or both.

For the purposes of this review, we will characterize hepaticprogenitor cells as either somatic hepatic progenitor cells(those cells that can be isolated from adult liver without chemicalinsult or partial hepatectomy), fetal hepatic progenitor cells(due to their origin and isolation from within the developingliver bud), or the previously characterized oval cell. The roleof oval cells in liver regeneration and their potential as hepaticprogenitors will be discussed in further detail. With the varyingdescriptions of unique hepatic progenitor cell populations,it is possible that overlap exists among differing populations.

There is currently a dichotomy between our understanding ofthe processes involved in stem cell differentiation and organdevelopment compared with the unanswered questions relatingto the postnatal role of stem or progenitor cell populationsas they persist into adulthood. Are the latter groups undifferentiatedstem cell populations that persist beyond the fetal period orare they de novo stem cells generated by signals from the adultsomatic cellular compartment? Further comprehension of characterizationand the process by which select stem or progenitor cells undergodifferentiation will provide greater insight into tissue developmentand organogenesis [11]. This understanding could also play arole in developing alternative cell therapy strategies. Thisreview focuses on multiple liver-derived stem or progenitorcell populations that have been isolated from liver tissue atvarious stages of development or in response to select injurymodels.